HIV/HCV Coinfection Update: From Testing to Treatment

HIV care providers tend to wear many hats: In addition to managing one of the most insidious infectious diseases in the history of humanity, an HIV care provider must also often manage a host of comorbid physical and mental conditions. In recent years, liver health -- particularly as it relates to hepatitis C (HCV) coinfection -- has increasingly become a prominent item on that comorbid condition list.

Meanwhile, within a stunningly brief span of time, our understanding of HIV/HCV coinfection has undergone a dramatic evolution. The landscape of coinfection risk, pathogenesis and treatment has utterly changed from just a few years ago.

To bring frontline HIV care providers up to date, I headed to the Mount Sinai School of Medicine in New York City and spoke with two of the foremost experts in HIV/HCV coinfection: Douglas Dieterich, M.D., a professor of medicine in Mount Sinai's division of liver diseases, and Daniel Fierer, M.D., an assistant professor of medicine in Mount Sinai's division of infectious diseases.

The Nature of the Epidemic

Myles Helfand: Where are we at right now, in terms of our understanding of HIV/HCV coinfection -- the numbers, the risks? What has changed in the past few years?

Douglas Dieterich: I'll start with the chronic, and I'll let Daniel handle the acute, because that's his area of expertise. The numbers of chronically infected patients are actually not that different: It's still 30+ percent of the HIV patients in the U.S. that are coinfected with hepatitis C, though that number may be getting a little bit higher. It also varies from clinic to clinic, from practice setting to practice setting.

What has changed are the recommendations for testing everybody for hepatitis C -- at least yearly now, instead of just once forever. That's actually something that should be done. Many places do it more frequently than yearly -- some approaching every three months, like they do for RPR [rapid plasma reagin, for syphilis], for instance.

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Daniel Fierer: Especially for very sexually active men who have sex with men. Active injection drug users, too.

Douglas Dieterich: Even active cocaine users. They don't have to inject.

I think what's also changed in the last five years, Daniel, is the men who have sex with men acute hepatitis C epidemic, which I'll let you discuss.

Daniel Fierer: Until we recognized that there is an emerging epidemic around the world -- and, certainly, in all the large cities in the U.S. -- of sexually transmitted hepatitis C in HIV-infected men who have sex with men, most of the hep C that we were seeing in HIV-infected people was hep C that they acquired quite a long time ago. There was a stable population -- about a quarter million coinfected people in the country -- that had long-term, chronic infection.

We noticed at Mt. Sinai in about 2006 -- and saw in the literature that the Europeans had noticed a few years earlier in Northern Europe -- that there were an increasing number of HIV-infected men who were getting hep C from sex. That recognition has resulted in a pretty clear guideline change in Europe and in the U.S. to recognize and test more frequently.

That's a very important thing to recognize: There is incident hep C now, where that was really pretty rare, unless you were taking care of active injection drug users or very heavy cocaine users.

Myles Helfand: There were initially a lot of assumptions made that, when we talked about sexual transmission in the context of HCV, we were talking about rougher sex, in which there's more likely to be blood contact. How true has that actually been proven to be?

Daniel Fierer: No one knows the exact answer to how hepatitis C is transmitted in sex that happens between men. There are many different kinds of things that happen during sex. The three case control studies that were done -- one we did here, one in London, and one in Germany -- all came up with somewhat different things as their highest risk factors associated with it.

To me, what that suggests is that there are a number of different ways that it can happen. Bleeding -- active, visible bleeding -- is not necessary. The Germans found that [rectal bleeding or pain was the largest risk factor], but that wasn't really found in London or here. I think, sure, if there's a lot of bleeding, that could do it. But we didn't have a lot of bleeding in our patients in New York -- and yet, they got hep C.

When (and How) to Test HIV-Infected Patients for HCV

Myles Helfand: You got a little bit into testing a moment ago. The recommendations changed pretty recently. This was as a direct result of these numbers?

Daniel Fierer: Yeah, exactly: recognition of a new risk group. The old suggestions were a little soft: "If you could be at risk for hep C, then you should test more often." But that didn't work all that well; even people who had injection drug use risks were not being tested frequently enough.

It comes down to: You have to be more conscious of it and do testing more. You have to consider what a risk might be and cast a broader net. We need more frequent testing and more awareness.

Myles Helfand: So, if you're an everyday HIV care provider, should you be testing all of your patients for HCV regularly?

Daniel Fierer: Yes, absolutely.

Myles Helfand: Or do you keep a look out for particular risk factors?

Douglas Dieterich: No, it takes too much time, and there's too much uncertainty -- and also a lack of admitting to risk factors, for the patients. Why even get into that? Just test them. It costs $8 for the antibody test.

Myles Helfand: And the frequency should be once a year? Or more, depending on --

Douglas Dieterich: Probably depending on their level of sexual activity. But officially, once a year.

Daniel Fierer: By comparison, there are no official guidelines for how often you test for syphilis. But if we're in the middle of a syphilis epidemic, and we have someone who is very sexually active, we test them quarterly -- whenever we see them. It's one of those things: You rely on your own clinical acumen, and the acumen of those around you.

I think that we have not done enough HCV tests. I've seen enough patients who have slipped through. You see them three years later and look back and say, "Oh, yeah. They had it three years ago; it just slipped through." There's a lot of that.

Douglas Dieterich: On the other hand, the antibody test is not completely adequate to diagnose somebody who has elevated liver enzymes and is very acutely infected. [It takes at least six weeks for the antibody to develop, sometimes a couple of months.]

People can be antibody-negative in the early stages of disease -- just like with HIV. When that's the case, then you need to bring them back in and either repeat the antibody or do the quantitative PCR for hepatitis C.

Daniel Fierer: The diagnosis of new hepatitis C infections that I've alluded to is tricky. There is no single test, so it is hard. Fortunately, HIV providers are fairly savvy on that. Experienced HIV providers are in a good position to get this, and to know that, if you suspect new infection, then you need to look at virus, for instance. You don't just say [to a sexually active MSM with a sore throat and fever], "Ah, it's strep throat. Go home." You get virus testing.

Douglas Dieterich: I think it's particularly important that HIV docs not ignore elevated liver enzymes. Particularly when they haven't really been elevated before.

Daniel Fierer: Yes.

Douglas Dieterich: That's something that, in large part, many HIV docs have been doing for many years: ignoring elevated liver enzymes without investigating fully what they might be. I think now is a time to start looking for hepatitis C.

You should assume, frankly, that anybody with new liver enzyme elevation and HIV who hasn't really switched their meds has got acute hepatitis C. That would be the number one diagnosis.

Daniel Fierer: I think that's a very good point. A very large proportion of people with a new ALT of, say, 400, may have hep C.

In fact, Doug, you made a couple of good pick-ups when patients have been started on new HIV antiretrovirals. Even in that setting, we've been almost fooled. Some savvy folks have picked up that, although starting efavirenz is known to cause an ALT elevation of 400, the elevations in their patients had, in fact, been the result of new hep C infection, and not due to the use of a new antiretroviral.

Myles Helfand: That speaks to the importance of regular HCV testing, especially when you're starting treatment.

Daniel Fierer: Yes. As Doug said, you can't stress too much that even a low-level ALT elevation can be the very beginning of something; we see this in new hep C infection. Bring them back for more testing -- not in the next three months, but in the next couple of weeks.

Douglas Dieterich: Acute hep C, in particular, doesn't have to have an ALT of 500, or 800, or 1,000; it could just be 100, which would often fall below many providers' radar screens, in terms of following it through and investigating the cause.

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